tbuckley/cabot-search huggingface dataset:
Abstract 14694: Effect of Saphenous Vein Graft on Multiple Arterial Grafting Survival
Authors: Justin Ren, colin royse, Stuart Boggett, Alistair Royse
Journal: Circulation (2022)

Introduction: Saphenous vein graft (SVG) is associated with increased mortality and adverse cardiac events compared to arterial conduits, but uncertainty exists whether its presence would influence the outcome in multiple arterial revascularization (MAG). Hypothesis: That use of SVG adversely affects survival even in the setting of MAG. Methods: All patients undergoing primary isolated CABG between June 2001 to Jan 2020 were identified through a national registry. Exclusion criteria were reoperations, concomitant or previous cardiac surgery, and the absence of arterial grafting. The primary outcome was long-term mortality reported as time-to-event from the date of the operation. We performed a complete case retrospective comparison between MAG and single arterial grafting (SAG). Additional analysis was performed in MAG patients with or without SVG.Propensity score matching (PSM) and Cox proportional hazard model were used with significance defined as two-tailed P&lt;0.05. Results: A total of 72,444 eligible patients had 58,629 (80.9%) males with 32,966 SAG (45.5%) and 39,478 MAG (54.5%). Two PSM was used to generate 29,354 matched pairs for SAG vs. MAG and 12,314 matched pairs for MAG with or without SVG. At a mean follow-up duration of 6.7 years, long-term mortality was significantly lower for MAG than SAG (HR, 0.89; 95% CI, 0.85-0.93). The cumulative Kaplan-Meier survival was 60.6% for SAG and 63.3% for MAG at 15 years postoperative, (P=0.002). In the comparison of MAG with or without SVG, the group without SVG (total arterial revascularization) had a lower risk of late mortality (HR, 0.91; 95% CI, 0.85-0.96). The interaction term analysis confirmed a significant effect for the presence of vein graft on the observed mortality when using MAG, (P=0.02). Sensitivity analyses produced consistent outcomes as the primary investigation. Conclusions: Multiple arterial grafting is associated with significantly improved long-term survival compared to single arterial grafting, and when total arterial revascularization was achieved, there was an incremental survival benefit.
Abstract 15615: The Association of Acute Kidney Injury With Angiotensin Converting Enzyme Inhibitor and Angiotensin Ii Receptor Blockers Use in Patients With Sars-cov-2
Authors: Aaron Douen, Marc Sukhoo-Pertab, Samuel Tan, Ryan Panetti, Wenchy Siu, Maryam Sadeghi, Fady Kaldas, Carly Bowser, Prakash Ramdass, Wesley Romney, George Juang, Aleksandre Toreli
Journal: Circulation (2022)

Introduction: Previous studies have suggested that SARS-CoV-2 causes microvascular inflammation and thrombosis, leading to microvascular angiopathy. A downstream sequela of microvascular angiopathy is AKI. Literature extensively describes the renoprotective effects of ACEI and ARB. Hypothesis: We hypothesize that using an ACEI/ARB in patients with SARS-CoV-2 is negatively associated with AKI. Methods: We conducted a retrospective chart review of patients 18 years and older who tested positive for SARS- CoV-2 using a polymerase chain reaction test between March 2020 and April 2021. Patients were divided into two groups, AKI, and non-AKI. The primary outcomes were all-cause mortality and hospitalization rate. The secondary outcomes were myocardial infarction, hypotension, intubation, use of vasopressors and ventricular tachycardia (VT). We used multivariate logistic regression to adjust for baseline characteristics. Results: We identified a total of 1,212 patients with AKI and 21,887 without AKI who tested positive for SARS-CoV-2. Incidence was 539 (44%) for all-cause mortality, 1144 (94.2%) for hospitalization, and 413 (34.6%) for patients taking ACEI/ARB. After logistic regression analysis, OR was 3.006 (95% Confidence Interval [CI]: 2.342-3.858; p&lt;0.001) for hospitalization, 7.359 (95% CI:5.191-10.433, p &lt;0.001) for all-cause mortality, and 1.034 (95% CI: 0.784-1.365; p&lt; 0.810) for patients taking ACEI/ARB. The AKI group had significantly increased adjusted OR for hypotension (p&lt; 0.001), calcium channel (p&lt;0.001) and beta-blocker (p&lt;0.038) use. Adjusted OR for all other secondary outcomes were not increased but not significant, including myocardial infarction (p&lt;0.697), VT (p&lt;0.184), vasopressor use (p&lt;0.113), and intubation (p&lt;0.096). Conclusions: This study suggests that ACEI/ARB use was not positively associated with AKI in patients with SARS-CoV-2, while calcium channel blocker and beta-blocker use were. A positive association between BB and CCB with AKI suggests that there should be a preference for ACEI/ARB in patients where all three medications are possible therapy options. Further studies are needed to confirm the association between ACE/ARB and AKI and rule out potential confounding variables.
Abstract 14719: Erk5 S496 Phosphorylation, but Not Erk5 Kinase Activation, Promotes Senescence-Associated Cell Growth (sacg) and Inflammation of Myeloid Cells and Atherosclerosis via Upregulating Sumoylation at a Novel Site (k518) on Nrf2 and Aryl Hydrocarbon Receptor
Authors: Sivareddy Kotla, Masaki Imanishi, Shengyu Li, Aijun Zhang, Kyung A Ko, Venkata Subrahman K Samanthapudi, Ling-Ling Lee, Joerg Herrmann, Steven Lin, Michael N Shoykhet, Ying H Shen, Keri Schadler, Minh T Nguyen, Anisha A Gupte, Cielito Reyes-Gibby, Sai-Ching Yeung, Nicolas L Palaskas, John P Cooke, Henry J Pownall, Momoko Yoshimoto, Keigi Fujiwra, Dale Hamilton, Jared K Burks, Guangyu Wang, Nhat Tu T Le, Junichi Abe
Journal: Circulation (2022)

Senescence induced by various stresses reprograms cancer cells to acquire senescence-associated (SA) cell growth (SACG), which allows them to escape senescence-induced cell cycle arrest with enhanced growth potential. ERK5 is a dual kinase-transcription factor, containing an N-terminal kinase domain and transactivation domains in the C-terminal half. Recent data have raised questions regarding the functional role of ERK5 kinase inhibitors in cancer and inflammatory diseases. We aimed to investigate how ERK5 reprograms myeloid cells (MC) to the SA secretory phenotype (SASP) and SACG, consequently leading to atherosclerosis (AthS). AthS was inhibited in ERK5 S496A knock-in (KI) mice. Single-cell analysis of p53 and Ki67 with imaging mass cytometry revealed three groups of MCs with different p53 and Ki67 expression patterns in the plaque. One group showed that p53 and Ki67 were co-expressed lineally, suggesting that this group of cells escaped from the growth-suppression effects of p53, which is also known as a senescence marker. The % of ERK5 S496A KI cells in this group was significantly lower than in wild-type (WT). Also, we found an increase of SA β-gal (SAβ-gal) + Ki67 + and 53BP1 + Ki67 + cells in bone narrow-derived macrophage (BMDMs) isolated from hypercholesterolemia (H-chol) WT mice, suggesting H-chol-induced MC SACG. MC SACG were significantly inhibited in ERK5 S496A KI mice, supporting the role of ERK5 S496 phosphorylation on SACG. RNA sequencing analysis identified the ERK5 S496 phosphorylation-dependent AHR induction by H-chol, and AHR depletion significantly inhibited SACG. We also discovered a critical effect of ERK5 S496 phosphorylation on SUMOylation at a novel site of NRF2 (i.e., K518), which inhibited NRF2 transcriptional activity without affecting ERK5 kinase activity and antagonized oxidized LDL (oxLDL)-induced SASP. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) inhibited oxLDL-induced ERK5 S496 phosphorylation, suggesting that ERK5 S496 phosphorylation was involved at least in part of the effects of these inhibitors. We have discovered a novel mechanism in which ERK5 S496 phosphorylation directly inhibits NRF2 activity by upregulating NRF2 K518 SUMOylation and AHR induction, subsequently inducing SACG and AthS.
Abstract 15359: Multi-Omics Integration Reveals Mechanosensitive Regulatory Pathways in Cardiac Fibroblasts
Authors: Jordan E Morningstar, Tyler Beck, Cortney Gensemer, Rachel Biggs, Taylor Petrucci, Lilong Guo, Ayesha Vohra, Le Mai, Melfry Gonzalez, Andrew Stoddard, Jaclyn Dunne, Russell A Norris
Journal: Circulation (2022)

Introduction: Regionalized myocardial fibrosis exists in the inferobasal myocardium of patients undergoing surgical repair for Mitral Valve Prolapse, and supports a process in which cells within mechanically stressed myocardial regions alter their phenotype in order to increase tissue stiffness, eventually causing establishment of a fibrotic scar. How cells behave in different fibromechanical environments is not currently well understood. Hypothesis: Integrating RNA Seq and ATAC Seq datasets will identify mechanosensitive regulatory pathways in cardiac fibroblasts. Methods: Primary human cardiac fibroblasts (HCFs) were cultured on stiff (TC Plastic, ~2GPa), as well as soft (2kPa) substrates coated with type 1 collagen. Following 48 hours in serum-free conditions, HCFs were lysed and subjected to immunofluorescence (IF), Western blotting (WB), RNA Seq, and ATAC Seq. Differential analysis of RNA Seq, and ATAC Seq data was performed, followed by an integration analysis which linked differentially expressed genes to chromatin that opened/closed within 10 kB. Finally, motif enrichment analysis was performed using the online bioinformatics package Homer. Results: IF and WB revealed that HCFs cultured on a stiff substrate expressed markers of fibroblast activation (alpha SMA, P&lt;0.0001), as well as increased amounts of Connexin 43 (P&lt;0.0001). Additionally, there were higher numbers of Ki-67 positive cells (7.2% vs 2.1% P=0.001). RNA Seq revealed differential changes in 4324 genes (FDR adjusted P&lt;0.05), several of which were subsequently validated using western blots. ATAC Seq identified 5855 chromatin regions which opened/closed in response to different mechanical environments in fibroblasts (adjusted P&lt;0.05). Integrating RNA Seq and ATAC Seq datasets revealed 803 Chromatin changes that fell within 10kb of differentially expressed genes, with a predicted enrichment of TEAD binding sites in differentially opened chromatin (P=1.0*10-40). Conclusions: The mechanical environment plays a major role in cellular phenotype and directly regulates chromatin organization and expression of pro-fibrotic genes, with a possible role for TEAD as a driver of fibroblast activation.
Abstract 15609: Neighborhood Socioeconomic Disparities in Infant Out-of-Hospital Cardiac Arrest
Authors: Aditya C Shekhar, Katie R Peeler, Jonathan M Marron, N. Clay Mann, Manu Madhok
Journal: Circulation (2022)

Introduction: More than half of all pediatric cardiac arrests involve children under 1 year of age, and intervention prior to the arrival of emergency medical services (EMS) is crucial to prevent irreversible injury in out-of-hospital cardiac arrest. Hypothesis: Given other cardiac arrest disparities, we hypothesize that pre-EMS CPR and outcomes for infant cardiac arrest differ across community socioeconomic status. Methods: We examined cardiac arrests in 2019 involving patients under 1 year of age contained within a nationally-representative EMS database in the United States (NEMSIS). Data collected included if pre-EMS CPR was performed, if return of spontaneous circulation (ROSC) was achieved, and the ZIP Code where the arrest took place. We grouped arrests based on the socioeconomic characteristics of the ZIP Code where the arrest took place. This allowed us to examine whether rates of pre-EMS CPR and ROSC varied according to community-level poverty. Results: A total of 3776 pediatric cardiac arrests met inclusion criteria (Table). Within the total sample, the overall pre-EMS CPR rate was 71.2%, and the overall ROSC achievement rate was 16.6%. Pre-EMS CPR and ROSC achievement were highest in communities where less than 5% of individuals were below the poverty line and were significantly lower in communities where more than 16% of individuals within a ZIP Code were below the poverty line (p&lt;.05). Conclusions: Our data show that two important predictors of cardiac arrest survival - Pre-EMS CPR and ROSC achievement - decline significantly as the percentage of individuals below the poverty line increase. Disparities across socioeconomic status may reflect decreased CPR awareness, underperforming systems of prehospital care, or worse infant baseline health statuses. Public health efforts aimed at infant cardiac arrest may see the most benefit when focusing on socioeconomically-disadvantaged communities.
Abstract 15366: Identifying Factors Associated With In-Hospital Mortality in Patients With Takatsubo Cardiomyopathy Utilizing a Machine Learning Algorithm
Authors: Sonu Abraham, Don Mathew, Aiswarya Rajendran, Anu Saji, Ajay K Mishra, Akil A Sherif
Journal: Circulation (2022)

Introduction: Takatsubo cardiomyopathy (TTS), also known as stress induced cardiomyopathy has a reported in-hospital mortality as high as 5% in the US. While overall risk factors have been previously reported, data regarding in-hospital contributors of mortality in TTS is lacking. In our study, we have utilized a Machine Learning (ML) algorithm to identify predictors of in-hospital mortality in patients with TTS. Hypothesis: Machine learning algorithms may be used to identify factors associated with in-hospital mortality in patients with TTS. Methods: We identified all unweighted hospitalizations with a primary diagnosis of TTS from 2016-2019 using International Classification of Diseases, Tenth Revision, diagnosis codes from the National Inpatient Sample (NIS). This is the largest publicly available database of US hospitalizations comprising a 20% stratified sample of all discharges. Data regarding demographics, hospital characteristics and associated diagnoses were abstracted and analyzed using a decision-tree ML algorithm. Results: We identified 7,517 patients who were hospitalized with a primary diagnosis of TTS. In this cohort, in-hospital mortality was noted to be 1.5%. 4 branches, 5 leaves and 8 nodes were identified by the decision-tree algorithm. In our model, the identified covariates associated with high in-hospital mortality were sudden cardiac arrest (p&lt;0.001), cardiogenic shock (p&lt;0.001), sepsis (p&lt;0.001) and Charlson Comorbidity burden (p&lt;0.001) in hierarchical order. Conclusions: ML based algorithms are being increasingly used to analyze clinical data. Our decision-tree ML algorithm was able to identify sudden cardiac arrest, cardiogenic shock, sepsis and Charlson comorbidity burden to be statistically significant predictors of in-hospital mortality amongst 77 other covariates.
Abstract 15223: Insights Into Myocardial Programming in SARS-CoV-2 Infection Using Spatial Transcriptomics
Authors: Maria Gabriela Gastanadui, Camilla Margaroli, Paul Benson, Chunyan Song, Liliana Viera, Dongqi Xing, James Wells, Rakesh Patel, Amit Gaggar, Gregory A Payne
Journal: Circulation (2022)

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is linked to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this has sparked growing controversy. Significance of myocardial infection also remains unclear. Hypothesis: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 with digital spatial transcriptomics. Methods: Autopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined paracrine effect of SARS-CoV-2 infection in cardiac tissue. Results: We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers (Figure 1). However, there was limited differential expression within the endothelium of larger coronary vessels. Conclusions: Our results highlight altered myocardial programming during severe COVID-19 that may be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis and endothelial activation as key drivers of cardiovascular events during COVID-19.
Abstract 14583: Large-Scale Real-World Experience of Cardiovascular and Renal Outcomes Among Hypotensive HFrEF Patients Treated With Angiotensin Receptor-Neprilysin Inhibitor
Authors: Chien-Yi Hsu, Hung-Yu Chang, Fa-Po Chung, Chung-Lieh Hung
Journal: Circulation (2022)

Background: Hypotension remains a major clinical scenario limiting the use of novel a ngiotensin receptor-neprilysin inhibitors (ARNi) treatment for heart failure with reduced ejection fraction (HFrEF). Hypothesis: To explore the mid- to long-term cardiovascular and renal outcomes of ARNi treatment in HFrEF patients from a large-scale real-world setting. Methods: In a multi-center survey, we categorized totally 7,772 HFrEF patients (≥20 years, baseline renal replacement excluded) according to blood pressure (hypotensive status as systolic blood pressure &lt;100mmHg) and ARNi use: Group1: Hypotensive/Non-ARNi users (n=488), Group 2: Hypotensive/ARNi users (n=311), Group 3: Normotensive/Non-ARNi users (n=4,700), and Group 4: Normotensive/ARNi users (n=2,273). Results: Hypotensive/Non-ARNi (Group 1) had smallest body mass and less likely to have baseline co-morbidity albeit higher prior myocardial infarction compared to other groups. Group 2 had slight yet significantly lower initiation dose of ARNi versus Group 4 (103.5±64.0 vs. 129.1±65.8 mg/daily, p&lt;0.001). During a median 1.82-year follow-up, both Group 2/Group 4 HFrEF patients had significantly lower all-cause mortality and cardiovascular (CV) death, and a composite of HF hospitalization/CV death in a fully adjusted model, with Group 3 had lower all-cause and CV death (Group 1 as reference) (Table 1). There were fewer though non-significant adjusted incident new onset renal replacement therapy (HD) for Group 2, 3 and 4 compared to Group 1. Kaplan-Meier survival curves showed significant survival differences among 4 groups for all cardiovascular/mortality endpoints (all log-rank p: &lt;0.001; worst in Group 1 vs. best survival in Group 4) except new onset HD (log-rank p: 0.29). Conclusion: Our current large-scale demonstrated that HFrEF patients with hypotension may still benefit from ARNi treatment. Hypotensive HFrEF patients should not be routinely excluded from ARNi use in a real-world setting.
Abstract 166: <u>Lung Parenchymal And Pleural Findings On Computed Tomography After Out-of-Hospital Cardiac Arrest</u>
Authors: Maranda Newton, Catherine Counts, Basar Sarikaya, Vasisht Srinivasan, Kelley R Branch, Nicholas J Johnson
Journal: Circulation (2022)

Introduction: Lung injury and the acute respiratory distress syndrome (ARDS) are common after out-of-hospital cardiac arrest (OHCA), but the imaging characteristics of lung parenchymal and pleural abnormalities in these patients have not been well-characterized. We aimed to describe the incidence of lung parenchymal and pleural findings among patients who had return of spontaneous circulation (ROSC) after OHCA who underwent computed tomography (CT) of the chest. Methods: This was a retrospective cohort study conducted at two academic hospitals from 2014 to 2019. We included adults with OHCA who received a head-to-pelvis or dedicated chest CT scan. The primary outcome was the incidence of lung parenchymal and pleural abnormalities. CT scans were overread by attending radiologists and lung parenchymal and pleural findings were categorized based on predefined criteria. Data are presented as absolute numbers and percentages. Results: We evaluated 243 eligible patients. Median age was 56 years, 32% were women, and 59% were Caucasian. An initial shockable rhythm was found in 29% and in 71 patients (30%) the etiology of arrest was cardiac. A total of 162 patients underwent head-to-pelvis CT and 81 patients had dedicated chest imaging. The median time from OHCA to CT scan was 2.7 (IQR 2.1-3.8) hours. A total of 190 (78%) of patients had abnormal lung parenchymal or pleural findings. The most common findings are depicted in Table 1. Conclusion: Over three-quarters of patients who survive to the hospital post OHCA have lung parenchymal or pleural abnormalities on CT, the most common of which are aspiration, pulmonary edema, and consolidation/pneumonia. Future planned research will characterize the clinical impact of these findings and whether early chest CT could identify patients at risk for ARDS.
Abstract 14699: Effect of Shear Stress on Arterial Inflammation and Development of Healed Plaque: A Comprehensive Shear Stress-Molecular Imaging Study Based on a Novel Multispectral Fluorescence Lifetime Imaging Catheter
Authors: Sunwon Kim, Hyeong Soo Nam, Dong Oh Kang, Jeongmoo Han, Hongki Yoo, Jin W Kim
Journal: Circulation (2022)

Introduction and Hypothesis: Endothelial shear stress (ESS) is the tangential force produced by luminal blood flow on arterial endothelium. Both high ESS and low ESS are known to have atherogenic effects, however, it remains poorly understood how these different forces influence coronary atherosclerosis. We evaluated the impact of ESS changes on biochemical and phenotypic difference of coronary atheroma, as assessed by a novel dual-modal optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm) in vivo in beating human coronary arteries. Methods and Results: We constructed a fully-integrated OCT and multispectral FLIm system based on a low-profile dual-modal imaging catheter. High-speed OCT-FLIm could be performed safely in patients undergoing coronary revascularization (Pullback speed: 10-20mm/sec). 3D artery model for computational fluid dynamics was reconstructed by fusion of OCT and angiography. We analyzed spatial associations between ESS and multispectral FLIm information: ch.3(542nm) = fibroatheroma with inflammation; ch.1 (390nm) = loose fibrous tissue (healed plaque). OCT-FLIm visualized coronary microstructure clearly and offered correctly-coregistered biochemical readouts of coronary atherosclerotic plaque in vivo in a label-free manner. Fibroatheromas with increased inflammation activity, as assessed by ch.3 FLIm, were found in low ESS area. On the other hands, high ESS area colocalized with regions with increased ch.1 lifetime, a FLIm signature of loose fibrous tissue (healed plaque). Based on a coregistered ESS-FLIm data, we found a statistically significant negative correlation between ESS and ch.3 lifetime (p&gt;0.001) and a positive correlation between ESS and ch.1 lifetime (p&gt;0.001). Conclusions: Low ESS was associated with lipid and macrophage infiltration whereas high ESS was associated with presence of loose fibrous tissue, a histologic marker of recent plaque disruption leading to rapid plaque progression. Our novel imaging strategy enabling comprehensive evaluation of complex interaction between ESS and biochemical phenotype of plaques is expected to enhance understanding of coronary atherosclerosis biology.